This invention relates to the preparation of a monohydrate of the lithium salt of cis 4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylate, and the hydrate per se.
Cyclic nucleotide phosphodiesterases (PDEs) represent a family of enzymes that hydrolyze the ubiquitous intracellular second messengers, adenosine 3xe2x80x2,5xe2x80x2-monophosphate (cAMP) and guanosine 3xe2x80x2,5xe2x80x2-monophosphate (cGMP) to their corresponding inactive 5xe2x80x2-monophosphate metabolites. At least ten distinct classes of PDE isozymes are believed to exist, each possessing unique physical and kinetic characteristics and each representing a product of a different gene family. These are distinguished using Arabic numerals 1-10.
A new approach toward improving the side effect profile of PDE inhibitors is to design a new generation of compounds that inhibit only a single PDE isozyme, i.e., the PDE isozyme that predominates in the tissue of cell of interest. The predominate cAMP PDE isozyme in immune and inflammatory cells is PDE4. It is also a major regulator of cAMP content in airway smooth muscle. Thus, selective inhibition of PdE4 elevates cAMP content in immune and inflammatory cells, as well as in airway smooth muscle. This leads to anti-inflammatory effects as well as bronchodilation. One or both of these therapeutic actions are useful in treating a variety of diseases, including, but not limited to asthma and COPD. PDE4 inhibitors, particularly PDE4-specific inhibitors are useful also in treating other diseases in the area of inflammation, (e.g., asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, rheumatoid arthritis), affects related to tumor necrosis factor and to cognition impairment (e.g., multi-infarct dementia, cognitive dysfunction, or stroke). This invention relates to a compound that is better tolerated than previous PDE4 inhibitors, namely cis-4-cyano-4-[3-(cyclopentyloxy)-4-metboxyphenyl]cyclohexane-1-carboxylic acid. More specifically this invention provides the hydrate of the lithium salt of this acid.